tbuckley/cabot-search huggingface dataset:
Reversible aberrancies in gut microbiome of moderate and late preterm infants: results from a randomized, controlled trial
Authors: Raakel Luoto, Anna Pärtty, Josef K. Vogt, Samuli Rautava, Erika Isolauri
Journal: Gut Microbes (2023)

The aim of this study was to obtain insight into the composition and function of the deviant gut microbiome throughout infancy in children born moderately and late preterm and their response to microbiome modulation. We characterized the longitudinal development of the gut microbiome from birth to the age of 12 months by metagenomic sequencing in 43 moderate and late preterm children participating in a randomized, controlled trial (ClinicalTrials.gov/no.NCT00167700) assessing the impact of a probiotic (Lactobacillus rhamnosus GG, ATCC 53,103, currently Lacticaseibacillus rhamnosus GG) and a prebiotic (galacto-oligosaccharide and polydextrose mixture, 1:1) intervention as compared to a placebo administered from 3 to 60 days of life. In addition, 9 full-term, vaginally delivered, breast-fed infants, who remained healthy long-term were included as references. Significant differences in taxonomy, but not in functional potential, were found when comparing the gut microbiome composition of preterm and full-term infants during the first month of life. However, the gut microbiome of preterm infants resembled that of full-term infants by 6 months age. Probiotic and prebiotic treatments were found to mitigate the shift in the microbiome of preterm infants by accelerating Bifidobacteria-dominated gut microbiome in beta diversity analysis. This study provides intriguing information regarding the establishment of the gut microbiome in children born moderately and late preterm, representing the majority of children born preterm. Specific pro- and prebiotics may reverse the proinflammatory gut microbiome composition during the vulnerable period, when the microbiome is low in resilience and susceptible to environmental exposure and simultaneously promotes immunological and metabolic maturation.
Engraftment of aging-related human gut microbiota and the effect of a seven-species consortium in a pre-clinical model
Authors: Huimin Ye, Tarini S. Ghosh, Cara M. Hueston, Klara Vlckova, Anna V. Golubeva, Niall P. Hyland, Paul W. O’Toole
Journal: Gut Microbes (2023)

Human aging is characterized by gut microbiome alteration and differential loss of gut commensal species associated with the onset of frailty. The administration of cultured commensal strains to replenish lost taxa could potentially promote healthy aging. To investigate the interaction of whole microbiomes and administered strains, we transplanted gut microbiota from a frail or healthy elderly subject into germ-free mice. We supplemented the frail-donor recipient group with a defined consortium of taxa (the "S7") that we identified by analyzing healthy aging subjects in our previous studies and whose abundance correlated with health-promoting dietary intervention. Inoculation with a frail or a healthy donor microbiome resulted in differential microbiota compositions in murine recipients 5 weeks post-transplantation. Fecal acetate levels were significantly higher in healthy donor recipient mice than in frail donor recipient mice after 4 weeks. However, the frailty-related phenotype was not replicated in recipient mice with single-dose microbiota transplantation from a healthy and a frail donor. Five S7 species colonized successfully in germ-free mice, with a relatively high abundance of Barnesiella intestinihominis and Eubacterium rectale. The engraftment of five S7 species in germ-free mice increased fecal acetate levels and reduced colon permeability and plasma TNF-ɑ concentration. Supplementation with the S7 in frail-microbiota recipient mice did not increase alpha-diversity but significantly increased the abundance of Barnesiella intestinihominis. S7 supplementation showed the potential for improving spatial reference memory in frail-microbiota recipient mice. Collectively, these data highlight the challenge of elderly microbiota engraftment in the germ-free mouse model but show promise for modulating the gut microbiome of frail elderly subjects by administering an artificial gut microbe consortium associated with healthy aging.
What Is a Physician? Navigating Incommensurable Spheres of Role Morality
Authors: Bryan Pilkington
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Spheres of Morality: The Ethical Codes of the Medical Profession DISCLOSURE STATEMENTNo potential conflict of interest was reported by the author(s).Notes1 Appelbaum et al. identify two types of therapeutic misconception: one occurs, “[w]hen participants express an incorrect belief that their individualized needs will determine assignment to treatment conditions or lead to modification of the treatment regimen” and the other occurs “[w]hen participants offer an unreasonable appraisal of the nature or likelihood of medical benefit from participation in the study, due to misconception of the nature of the research enterprise” (Appelbaum, Lidz, and Grisso Citation2004).2 This discussion merely offers anecdotal support for my claims and does not constitute a definitive objection to Doernberg and Truog’s analysis. However, it does suggest that more needs to be said in defense of the spheres in response to how the roles of physicians have been thought of from the perspective of those who are cared for or researched upon. This portion of the discussion focuses on only two, but two very important, spheres.Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Use Dignity, Not Its Parasites or Offspring
Authors: Charles Foster
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Spheres of Morality: The Ethical Codes of the Medical Profession DISCLOSURE STATEMENTNo potential conflict of interest was reported by the author(s).Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Response to Open Peer Commentaries on “Public Engagement through Inclusive Deliberation: The Human Genome International Commission and Citizens’ Juries”
Authors: Naomi Scheinerman
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Public Engagement with Human Germline Editing Requires SpecificationInclusion by Invitation Only? Public Engagement beyond Deliberation in the Governance of Innovative BiotechnologyVarieties of Citizen Engagement in Deliberation about BiotechnologyWhat Kind of Popular Participation Does Bioethics Need? Clarifying the Ends of Public Engagement through Randomly Selected Mini-PublicsPublic Engagement through Inclusive Deliberation: The Human Genome International Commission and Citizens’ JuriesIn Defense of Expert Knowledge in Bioethical Discussions on Human Genome EditingIt Takes Two to Tango: Fostering Engagement Within Citizen JuriesNot All Publics Are the Same—A Note on Power, Diversity, and Lived Expertise in Public Deliberation DISCLOSURE STATEMENTNo potential conflict of interest was reported by the author(s).Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Cost of Exempting Sole Orphan Drugs From Medicare Negotiation
Authors: Matthew Vogel, Olivia Zhao, William B. Feldman, Amitabh Chandra, Aaron S. Kesselheim, Benjamin N. Rome
Journal: JAMA Internal Medicine (2023)

Importance The Inflation Reduction Act (IRA) requires Medicare to negotiate prices for some high-spending drugs but exempts drugs approved solely for the treatment of a single rare disease. Objective To estimate Medicare spending and global revenues for drugs that might have been exempt from negotiation from 2012 to 2021. Design, Setting, and Participants This cross-sectional study analyzed drugs that met the IRA threshold for price negotiation (Medicare spending &amp;amp;gt;$200 million/y) in any year from 2012 to 2021 and had an Orphan Drug Act designation. We stratified drugs into 4 mutually exclusive categories: approved for a single rare disease (sole orphan), approved for multiple rare diseases (multiorphan), initially approved for a rare disease and subsequently approved for a nonrare disease (orphan first), and initially approved for a nonrare disease and subsequently approved for a rare disease (non–orphan first). Outcomes The primary outcomes were the number of sole orphan drugs, estimated Medicare spending on those drugs from 2012 to 2021, and global revenue since launch. Results Among 282 drugs, 95 (34%) were approved to treat at least 1 rare disease, including 25 sole orphan drugs (26%), 20 multiorphan drugs (21%), 13 orphan first drugs (14%), and 37 non–orphan first drugs (39%). From 2012 to 2021, Medicare spending on sole orphan drugs increased from $3.4 billion to $10.0 billion. Each year, a median (IQR) of $2.5 ($1.9-$2.6) billion in Medicare spending would have been excluded from price negotiation because of the sole orphan exemption. The cumulative global revenue of the median (IQR) sole orphan drug was $11 ($6.6-$19.2) billion. Conclusions and Relevance The sole orphan exemption will exclude billions of dollars of Medicare drug spending from price negotiation. The high level of global revenues achieved by these drugs, however, suggests that special exemption is unnecessary for them to achieve financial success. Congress could consider removing the sole orphan exemption to obtain additional savings for patients and taxpayers and to eliminate any potential disincentive for developing additional indications for these drugs.
Discrepancies in Estimating Excess Death by Political Party Affiliation During the COVID-19 Pandemic—Reply
Authors: Jacob Wallace, Paul Goldsmith-Pinkham, Jason L. Schwartz
Journal: JAMA Internal Medicine (2023)

In Reply A letter from O’Mahen provides valuable context and commentary on our article, “Excess Death Rates for Republican and Democratic Registered Voters in Florida and Ohio During the COVID-19 Pandemic.”1
Incorporation of genetic testing into the diagnostic algorithms of PALF: The time is now
Authors: James E. Squires, Simon P. Horslen
Journal: Hepatology (2023)

Division of Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Pittsburgh of the University of Pittsburgh Medical Center Correspondence James E Squires, Division of Gastroenterology, Hepatology and Nutrition Children’s Hospital of Pittsburgh One Children’s Hospital Drive, 6th Floor FP 4401 Penn Avenue Pittsburgh PA 15224. Email: [email protected]
Error in Figure
Journal: JAMA Pediatrics (2023)

Yuting Wang, MD; Ivan D. Florez, MD, MSc, PhD; Rebecca L. Morgan, MPH, PhD; Farid Foroutan, PhD; Yaping Chang, PhD; Holly N. Crandon, MBiotech; Dena Zeraatkar, MSc, PhD; Malgorzata M. Bala, MD, PhD; Randi Q. Mao, MD; Brendan Tao, MD; Shaneela Shahid, MD, MSc; Xiaoqin Wang, PhD; Joseph Beyene, PhD; Martin Offringa, MD, PhD; Philip M. Sherman, MD; Enas El Gouhary, MD; Gordon H. Guyatt, MD, MSc; Behnam Sadeghirad, PharmD, MPH, PhD
Genetically encoding multiple functionalities into extracellular vesicles for the targeted delivery of biologics to T cells
Authors: Devin M. Stranford, Lacy M. Simons, Katherine E. Berman, Luyi Cheng, Beth N. DiBiase, Michelle E. Hung, Julius B. Lucks, Judd F. Hultquist, Joshua N. Leonard
Journal: Nature Biomedical Engineering (2023)
Beyond Incommensurability and Appropriateness: Integrating the <i>Telos</i> of Medicine and Addressing Compartmentalization in the Spheres of Morality Framework
Authors: Ariel Guersenzvaig
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Spheres of Morality: The Ethical Codes of the Medical Profession DISCLOSURE STATEMENTNo potential conflict of interest was reported by the author(s).Notes1 All unreferenced quotes are from Doernberg and Truog (Citation2023).2 In this way, they dispel any potential charge based on what has become known as the problem of dirty hands, a situation where putative correct action may come into conflict with widely accepted moral principles (Coady Citation2023).3 I teach at an engineering school, indulge me with this paradigmatic example.Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Low-Dose Methotrexate and Serious Adverse Events Among Older Adults With Chronic Kidney Disease
Authors: Flory T. Muanda, Peter G. Blake, Matthew A. Weir, Fatemeh Ahmadi, Eric McArthur, Jessica M. Sontrop, Brad L. Urquhart, Richard B. Kim, Amit X. Garg
Journal: JAMA Network Open (2023)

Low-dose methotrexate is used to treat rheumatoid arthritis and psoriasis. Due to its kidney elimination, better evidence is needed to inform its safety in adults with chronic kidney disease (CKD).To compare the 90-day risk of serious adverse events among adults with CKD who started low-dose methotrexate vs those who started hydroxychloroquine and to compare the risk of serious adverse events among adults with CKD starting 2 distinct doses of methotrexate vs those starting hydroxychloroquine.This retrospective, population-based, new-user cohort study was conducted in Ontario, Canada (2008-2021) using linked administrative health care data. Adults aged 66 years or older with CKD (defined as an estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2 but not receiving dialysis) who started low-dose methotrexate (n = 2309) were matched 1:1 with those who started hydroxychloroquine.Low-dose methotrexate (5-35 mg/wk) vs hydroxychloroquine (200-400 mg/d).The primary outcome was a composite of serious adverse events: a hospital visit with myelosuppression, sepsis, pneumotoxic effects, or hepatotoxic effects within 90 days of starting the study drug. Prespecified subgroup analyses were conducted by eGFR category. Propensity score matching was used to balance comparison groups on indicators of baseline health. Risk ratios (RRs) were obtained using modified Poisson regression, and risk differences (RDs) using binomial regression.In a propensity score-matched cohort of 4618 adults with CKD (3192 [69%] women; median [IQR] age, 76 [71-82] years), the primary outcome was higher in patients who started low-dose methotrexate vs those who started hydroxychloroquine (82 of 2309 [3.55%] vs 40 of 2309 [1.73%]; RR, 2.05 (95% CI, 1.42-2.96); RD, 1.82% [95% CI, 0.91%-2.73%]). In subgroup analysis, the risks increased progressively at lower eGFR (eg, eGFR <45 mL/min/1.73 m2: RR, 2.79 [95% CI, 1.51-5.13]). In the secondary comparison with hydroxychloroquine, methotrexate users at 15 to 35 mg/wk had a higher risk of the primary outcome.In this cohort of 4618 older patients with CKD, the 90-day risk of serious adverse events was higher among those who started low-dose methotrexate than those who started hydroxychloroquine. If verified, these risks should be balanced against the benefits of low-dose methotrexate use.
Occupying Multiple Practical Identities instead of Moving between the Moral Spheres: An Alternative Perspective on Physicians’ Professional Ethics
Authors: Henk Jasper van Gils-Schmidt, Sabine Salloch
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Spheres of Morality: The Ethical Codes of the Medical Profession DISCLOSURE STATEMENTNo potential conflict of interest was reported by the author(s).Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Effect of Personalized Risk-Reduction Strategies on Cognition and Dementia Risk Profile Among Older Adults
Authors: Kristine Yaffe, Eric Vittinghoff, Sascha Dublin, Carrie B. Peltz, Lynn E. Fleckenstein, Dori E. Rosenberg, Deborah E. Barnes, Benjamin H. Balderson, Eric B. Larson
Journal: JAMA Internal Medicine (2023)

Importance Modifiable risk factors are hypothesized to account for 30% to 40% of dementia; yet, few trials have demonstrated that risk-reduction interventions, especially multidomain, are efficacious. Objective To determine if a personalized, multidomain risk reduction intervention improves cognition and dementia risk profile among older adults. Design, Setting, and Participants The Systematic Multi-Domain Alzheimer Risk Reduction Trial was a randomized clinical trial with a 2-year personalized, risk-reduction intervention. A total of 172 adults at elevated risk for dementia (age 70-89 years and with ≥2 of 8 targeted risk factors) were recruited from primary care clinics associated with Kaiser Permanente Washington. Data were collected from August 2018 to August 2022 and analyzed from October 2022 to September 2023. Intervention Participants were randomly assigned to the intervention (personalized risk-reduction goals with health coaching and nurse visits) or to a health education control. Main Outcomes and Measures The primary outcome was change in a composite modified Neuropsychological Test Battery; preplanned secondary outcomes were change in risk factors and quality of life (QOL). Outcomes were assessed at baseline and 6, 12, 18, and 24 months. Linear mixed models were used to compare, by intention to treat, average treatment effects (ATEs) from baseline over follow-up. The intervention and outcomes were initially in person but then, due to onset of the COVID-19 pandemic, were remote. Results The 172 total participants had a mean (SD) age of 75.7 (4.8) years, and 108 (62.8%) were women. After 2 years, compared with the 90 participants in the control group, the 82 participants assigned to intervention demonstrated larger improvements in the composite cognitive score (ATE of SD, 0.14; 95% CI, 0.03-0.25; P = .02; a 74% improvement compared with the change in the control group), better composite risk factor score (ATE of SD, 0.11; 95% CI, 0.01-0.20; P = .03), and improved QOL (ATE, 0.81 points; 95% CI, −0.21 to 1.84; P = .12). There were no between-group differences in serious adverse events (24 in the intervention group and 23 in the control group; P = .59), but the intervention group had greater treatment-related adverse events such as musculoskeletal pain (14 in the intervention group vs 0 in the control group; P &amp;amp;lt; .001). Conclusions and Relevance In this randomized clinical trial, a 2-year, personalized, multidomain intervention led to modest improvements in cognition, dementia risk factors, and QOL. Modifiable risk-reduction strategies should be considered for older adults at risk for dementia. Trial Registration ClinicalTrials.gov Identifier: NCT03683394
We Need Role Fidelity and Integrity to Avoid Moral Compartmentalization, Not Sphere or Role Moralities
Authors: Lauris Christopher Kaldjian
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Spheres of Morality: The Ethical Codes of the Medical Profession DISCLOSURE STATEMENTNo potential conflict of interest was reported by the author(s).Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
An Opportunity to Reconsider Fiduciary Framing in Medicine
Authors: Jennifer L. Herbst
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Spheres of Morality: The Ethical Codes of the Medical Profession DISCLOSURE STATEMENTNo potential conflict of interest was reported by the author(s).Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
What Kind of Popular Participation Does Bioethics Need? Clarifying the Ends of Public Engagement through Randomly Selected Mini-Publics
Authors: Jin K. Park, Samuel Bagg, Anna C. F. Lewis
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Public Engagement through Inclusive Deliberation: The Human Genome International Commission and Citizens’ JuriesThis article is referred to by:Response to Open Peer Commentaries on “Public Engagement through Inclusive Deliberation: The Human Genome International Commission and Citizens’ Juries” DISCLOSURE STATEMENTNo potential conflict of interest was reported by the author(s).Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
A population-level digital histologic biomarker for enhanced prognosis of invasive breast cancer
Authors: Mohamed Amgad, James M. Hodge, Maha A. T. Elsebaie, Clara Bodelon, Samantha Puvanesarajah, David A. Gutman, Kalliopi P. Siziopikou, Jeffery A. Goldstein, Mia M. Gaudet, Lauren R. Teras, Lee A. D. Cooper
Journal: Nature Medicine (2023)
TANGO: a placebo-controlled randomized phase 2 study of efficacy and safety of the anti-tau monoclonal antibody gosuranemab in early Alzheimer’s disease
Authors: Melanie Shulman, Jessica Kong, John O’Gorman, Elena Ratti, Rajasimhan Rajagovindan, Louis Viollet, Ellen Huang, Sanjiv Sharma, Annie M. Racine, Julie Czerkowicz, Danielle Graham, Yumeng Li, Heike Hering, Samantha Budd Haeberlein
Journal: Nature Aging (2023)
In vivo reprogramming leads to premature death linked to hepatic and intestinal failure
Authors: Alberto Parras, Alba Vílchez-Acosta, Gabriela Desdín-Micó, Sara Picó, Calida Mrabti, Elena Montenegro-Borbolla, Céline Yacoub Maroun, Amin Haghani, Robert Brooke, María del Carmen Maza, Cheyenne Rechsteiner, Fabrice Battiston, Clémence Branchina, Kevin Perez, Steve Horvath, Claire Bertelli, Christine Sempoux, Alejandro Ocampo
Journal: Nature Aging (2023)
Competing Duties and Professional Roles
Authors: Rosamond Rhodes
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Spheres of Morality: The Ethical Codes of the Medical Profession DISCLOSURE STATEMENTNo potential conflict of interest was reported by the author(s).Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
X-CHIME enables combinatorial, inducible, lineage-specific and sequential knockout of genes in the immune system
Authors: Martin W. LaFleur, Ashlyn M. Lemmen, Ivy S. L. Streeter, Thao H. Nguyen, Lauren E. Milling, Nicole M. Derosia, Zachary M. Hoffman, Jacob E. Gillis, Qin Tjokrosurjo, Samuel C. Markson, Amy Y. Huang, Praju V. Anekal, Paula Montero Llopis, W. Nicholas Haining, John G. Doench, Arlene H. Sharpe
Journal: Nature Immunology (2023)
A Decolonial Critique to the Spheres of Morality in the Medical Profession
Authors: Gabriela Arguedas-Ramirez
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Spheres of Morality: The Ethical Codes of the Medical Profession DISCLOSURE STATEMENTNo potential conflict of interest was reported by the author(s).Notes1 See for instances, these cases reported by the Center for Constitutional Rights https://ccrjustice.org/torture-us-prisons.2 For instance, ethical issues related to redistributive justice (managing to provide the best care possible, under continuous financial pressure in the context of national economic crisis).Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
It Takes Two to Tango: Fostering Engagement Within Citizen Juries
Authors: Brenda Bogaert, Ralf J. Jox
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Public Engagement through Inclusive Deliberation: The Human Genome International Commission and Citizens’ JuriesThis article is referred to by:Response to Open Peer Commentaries on “Public Engagement through Inclusive Deliberation: The Human Genome International Commission and Citizens’ Juries” DISCLOSURE STATEMENTNo potential conflict of interest was reported by the author(s).Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.